The ultimate goal of this program is to obtain data which can be used to determine the present or potential role of inhibitors of environmental chemical carcinogens in preventing neoplasia. Persuant to this goal are several major objectives. The first is to identify inhibitors of chemical carcinogenesis. The second is to determine the mechanisms of inhibition by compounds having an inhibitory effect. The third is to determine chemical characteristics which control the ability of compounds to inhibit chemical carcinogenesis with the further goal of producing more effective inhibitors (higher potency and less toxicity). The fourth is to determine conditions under which inhibition occurs. The first part of this renewal is a study of reactions between phenolic antioxidants such as butylated hydroxyanisole (BHA) and direct acting carcinogens. Efforts will be made to relate any such reactions to the capacity of these antioxidants to inhibit carcinogen-induced neoplasia. The second part focuses on two new groups of inhibitors, coumarins and aryl isothiocyanates. Efforts will be made to determine their mechanism of inhibition, relationships between chemical structure and inhibiting activity, and conditions under which inhibition occurs.